AAV-ie enables safe and efficient gene transfer to inner ear cells

被引：0
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作者：
Fangzhi Tan
Cenfeng Chu
Jieyu Qi
Wenyan Li
Dan You
Ke Li
Xin Chen
Weidong Zhao
Cheng Cheng
Xiaoyi Liu
Yunbo Qiao
Bing Su
Shuijin He
Chao Zhong
Huawei Li
Renjie Chai
Guisheng Zhong
机构：
[1] ShanghaiTech University,iHuman Institute
[2] ShanghaiTech University,School of Life Science and Technology
[3] University of the Chinese Academy of Sciences,MOE Key Laboratory for Developmental Genes and Human Disease, Institute of Life Sciences, Jiangsu Province High
[4] Southeast University,Tech Key Laboratory for Bio
[5] Nantong University,Medical Research
[6] Fudan University,Co
[7] ShanghaiTech University,innovation Center of Neuroregeneration, Jiangsu Key Laboratory of Neuroregeneration
[8] Chinese Academy of Sciences,ENT Institute and Otorhinolaryngology Department of Affiliated Eye and ENT Hospital, Key Laboratory of Hearing Medicine of NHFPC, Shanghai Engineering Research Centre of Cochlear Implant, State Key Laboratory of Medical Neurobio
[9] Jiangsu Provincial Key Medical Discipline (Laboratory),School of Physical Science and Technology
[10] Research Institute of Otolaryngology,Shanghai Institute of Ceramics
[11] Guangzhou University,Department of Otolaryngology Head and Neck Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School
[12] Chinese Academy of Science,Precise Genome Engineering Center, School of Life Sciences
[13] Capital Medical University,Institute for Stem Cell and Regeneration
来源：
Nature Communications | / 10卷
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摘要：
Hearing loss is the most common sensory disorder. While gene therapy has emerged as a promising treatment of inherited diseases like hearing loss, it is dependent on the identification of gene delivery vectors. Adeno-associated virus (AAV) vector-mediated gene therapy has been approved in the US for treating a rare inherited eye disease but no safe and efficient vectors have been identified that can target the diverse types of inner ear cells. Here, we identify an AAV variant, AAV-inner ear (AAV-ie), for gene delivery in mouse inner ear. Our results show that AAV-ie transduces the cochlear supporting cells (SCs) with high efficiency, representing a vast improvement over conventional AAV serotypes. Furthermore, after AAV-ie-mediated transfer of the Atoh1 gene, we find that many SCs trans-differentiated into new HCs. Our results suggest that AAV-ie is a useful tool for the cochlear gene therapy and for investigating the mechanism of HC regeneration.
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